Typically, COPD is encountered in smokers. The disease is characterized by chronic inflammation of the small airways (<2 mm) which unavoidably results in tissue reconstruction and irreparable narrowing (obstruction) of this portion of the airways.
Detailed tissue examination of these small airways shows increased production of mucus, increase in muciferous goblet cells, smooth muscle hypertrophy as well as infiltration with pigment-charged macrophages and CD8 positive T lymphocytes. As this process continues, tissue reconstruction and an increased deposition of connective tissue fibers occur.
Pathophysiologically, it is the inflammation which is most important. It is characterized by an infiltration of the small airways tissue with neutrophile granulocytes, macrophages, and lymphocytes. This infiltration into the tissue is facilitated by the production of proteases by leucocytes. Mediators are produced within the tissue which promote mucus formation, stimulate muscle cells and support the generation of connective tissue (collagen) fibers by fibroblasts.
In examinations of the respiratory mechanic, COPD shows a decreased maximal expiratory flow (FEV1) and a slow forced emptying of the lungs. COPD is often associated with chronic bronchitis and emphysema. However, these two diseases can be clearly distinguished from COPD.
Clinically, chronic bronchitis is defined by a chronic productive cough for at least 3 months per year in at least 2 successive years. This disease is characterized by common bacterial infections and it can but does not necessarily lead to an irreversible obstruction.
Emphysema is defined as an irreversible dilatation of the airways distal of the terminal bronchia caused by degradation of the alveolar septs associated with a degradation of elastic fibers. Emphysema is not accompanied by fibrosis.
Thus, COPD may be differentiated as an entity from chronic bronchitis and emphysema although COPD may be accompanied by these two diseases.
Predominantly, COPD affects the small airways while chronic bronchitis occurs in the large and medium airways and emphysema in the alveoles.
COPD is an irreversible process resulting in tissue rearrangements accompanied by a fibrosis (an increase in fibers). Chronic bronchitis does not result in tissue rearrangements. In emphysema, destruction of the alveolar septs, is observed.
An increase in neutrophile granulocytes, macrophages, and CD8 cells in the small airways has been found to be typical in COPD. All inflammatory cells are involved in chronic bronchitis while leucocytes are of no major importance in emphysema.
It is known from EP 0 352 412 to use esters of retinoic acid and/or an ester of retinol in the preparation form of an aerosol inhalant for topical application by inhalation to prevent and treat mucous membrane disorders of the tracheo-bronchial tract in humans and animals. These so-called bronchitides include acute and chronic bronchitides which show no obstruction. For example, the majority of smokers suffers from chronic bronchitis without showing airway obstruction and thus COPD. Bronchiectases are irreversible, cylindric, saccular or varicoid dilatations of the bronchia, a syndrome not belonging to the chronic obstructive disease, COPD.
Therefore, the mucous membrane disorders of the tracheo-bronchial tract mentioned in EP 0 352 412 do not belong to the diseases to be subsumed under the term COPD. They differ from COPD particularly in that they do not show the irreversible obstruction typical for COPD.
Up to now, COPD has been treated for example by administration of β-adrenergics/anticholinergics, theophyllin, and/or glucocorticoids. Disadvantages of the above-mentioned medicaments are that their activity is only symptomatic and that they have no effect on the fatal course of COPD. Spasmolytics have a life shortening effect. Theophyllin causes arrhytmias. An important side effect of glucocorticoids is osteoporosis.